Vitamin D Status and Immune-inflammatory Status in Different UK Populations With COVID-19 Infection

Covid19 Clinical Trial

Official title:

Retrospective Pilot Study of Vitamin D Status and Immune-inflammatory Status in Different UK Populations With COVID-19 Infection

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04519034
• Other study ID #: 285176
• Status: Completed
• Start date: September 1, 2020
• Est. completion date: March 31, 2021

Study information

• Verified date: July 2021
• Source: Guy's and St Thomas' NHS Foundation Trust
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Hypothesis: Serum Vitamin D (25(OH)D) is significantly lower in severe versus non-severe COVID-19 infections and that this is a function of ethnicity. There is an association between vitamin D status and various cytokines (pro-inflammatory molecules).

The primary objective of this research is to provide a snap shot of vitamin D status in patients from the South-East London area by age, sex, ethnicity and BMI and demonstrate ethnic differences in vitamin D status as well as its associations with severe vs non-severe COVID-19 infections.

The secondary objective is to determine if there is an association between vitamin D status and various cytokines (pro-inflammatory molecules) and severity of disease.

Description:

Worldwide there has been over 6 million cases and 380,810 deaths from Coronavirus 2019 (COVID-19) (ECDC June 2020). According to the European Centre for Disease Prevention and Control (ECDC) risk factors for critical illness include elderly people above 70 years of age, and people with underlying conditions such as hypertension, diabetes, cardiovascular disease, chronic respiratory disease, immune compromised status and obesity (73.4% of critically ill patients with BMI 30-40). In addition, in the UK 32% of critically ill COVID-19 patients are of Black or Asian ethnic-minority background (ICNARC April 10th, 2020). There is therefore an urgent need to fully understand the risk factors for severe COVID-19 infection and find an effective treatment. In COVID-19 infection those patients that required intensive care treatment have high circulating cytokines and chemokines TNF-α, IL-2, IL-6, IL-7, IL-9, IL-17, IFN-γ, MCP-1 and MIP-1α. Severe COVID-19 infection appears therefore to be associated with a damaging hyperinflammation state. In addition to a dysregulated cytokine response there is also dysregulation of immune cell populations in COVID-19 infection. For example, there is low T regs, NK cell and CD8+ and CD4+ T cells in severe COVID-19 infection. Moreover, CD8+ T cells appear to be an independent predictor for COVID-19 severity and treatment efficacy.

Other than genetic factors, e.g. HLA, which may predispose to severe COVID-19, vitamin D (25(OH)D) may be important for several reasons. Firstly because 25(OH)D inadequacy is prevalent in European and US older adults (>60 years), Black and Asian minority ethnic population groups and in those with a high BMI. Secondly because 25(OH)D is known to have important immunoregulatory roles e.g. in downregulating pro-inflammatory cytokines TNF-α, IL-1, IL-2, IL-6, IL-8, IL-17, IFN-γ and upregulating anti-inflammatory TGFβ and IL-10. 25(OH)D also promotes Treg and effector CD8+ T cell differentiation and expansion. Furthermore, 25(OH)D has a role in preventing and reducing human respiratory infections e.g. influenza and in experimental animals is positively associated with virus specific CD8+ T cells. Vitamin D may also be an important modulator of hyperinflammatory response in patients with Covid-19 infection through cytokine storm suppression.

As part of the Government's response to Covid-19, Public Health England has re-issued existing advice on vitamin D: https://www.nhs.uk/conditions/vitamins-and-minerals/vitamin-d/ This study will provide important information on vitamin D status as a possible risk factor in relation to COVID-19 infection in UK elderly and ethnic minority populations. Furthermore, the data generated could also have important implications for future supplementation and or vaccination strategies for COVID-19.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27628
• Est. completion date: March 31, 2021
• Est. primary completion date: January 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 100 Years

Eligibility

Inclusion Criteria:

• All patients tested for vitamin D and Covid-19

Exclusion Criteria:

• not applicable

Related Conditions & MeSH terms

• Covid19
• Infection

Intervention

Other:
• no intervention
There will be no intervention

Locations

Country	Name	City	State
United Kingdom	GSTT NHS Trust	London

Sponsors (1)

Lead Sponsor	Collaborator
Guy's and St Thomas' NHS Foundation Trust

Country where clinical trial is conducted

United Kingdom, 

References & Publications (8)

Bergman P, Lindh AU, Björkhem-Bergman L, Lindh JD. Vitamin D and Respiratory Tract Infections: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. PLoS One. 2013 Jun 19;8(6):e65835. doi: 10.1371/journal.pone.0065835. Print 2013. Review. — View Citation

Daneshkhah A, Agrawal V, Eshein A, Subramanian H, Roy HK, Backman V. Evidence for possible association of vitamin D status with cytokine storm and unregulated inflammation in COVID-19 patients. Aging Clin Exp Res. 2020 Oct;32(10):2141-2158. doi: 10.1007/s40520-020-01677-y. Epub 2020 Sep 2. — View Citation

Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5. Epub 2020 Jan 24. Erratum in: Lancet. 2020 Jan 30;:. — View Citation

Martineau AR, Jolliffe DA, Greenberg L, Aloia JF, Bergman P, Dubnov-Raz G, Esposito S, Ganmaa D, Ginde AA, Goodall EC, Grant CC, Janssens W, Jensen ME, Kerley CP, Laaksi I, Manaseki-Holland S, Mauger D, Murdoch DR, Neale R, Rees JR, Simpson S, Stelmach I, Trilok Kumar G, Urashima M, Camargo CA, Griffiths CJ, Hooper RL. Vitamin D supplementation to prevent acute respiratory infections: individual participant data meta-analysis. Health Technol Assess. 2019 Jan;23(2):1-44. doi: 10.3310/hta23020. — View Citation

Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ; HLH Across Speciality Collaboration, UK. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020 Mar 28;395(10229):1033-1034. doi: 10.1016/S0140-6736(20)30628-0. Epub 2020 Mar 16. — View Citation

O'Neill LA, Kishton RJ, Rathmell J. A guide to immunometabolism for immunologists. Nat Rev Immunol. 2016 Sep;16(9):553-65. doi: 10.1038/nri.2016.70. Epub 2016 Jul 11. Review. — View Citation

Shen L, Li S, Zhu Y, Zhao J, Tang X, Li H, Xing H, Lu M, Frederick C, Huang C, Wong G, Wang C, Lan J. Clinical and laboratory-derived parameters of 119 hospitalized patients with coronavirus disease 2019 in Xiangyang, Hubei Province, China. J Infect. 2020 Jul;81(1):147-178. doi: 10.1016/j.jinf.2020.03.038. Epub 2020 Apr 10. — View Citation

Surman SL, Jones BG, Woodland DL, Hurwitz JL. Enhanced CD103 Expression and Reduced Frequencies of Virus-Specific CD8(+) T Cells Among Airway Lymphocytes After Influenza Vaccination of Mice Deficient in Vitamins A + D. Viral Immunol. 2017 Dec;30(10):737-743. doi: 10.1089/vim.2017.0086. Epub 2017 Nov 13. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Collecting vitamin D results in patients from the South-East London area together with age, sex, ethnicity and BMI and other relevant laboratory results.	All vitamin D results performed by the Nutristasis Unit at St. Thomas' since January 2020 (N= ~15000) together with age, weight and height if available, ethnicity and other relevant laboratory markers (Ca, adjusted calcium, PTH, Mg, phosphate, liver and renal profile, Covid-19 screening, CRP, Haematinics, FBC) if they were tested within two weeks of the sample being measured for vitamin D will be acquired. The results of this audit will provide a snap shot of vitamin D status in patients from the South-East London area by age, sex, ethnicity and BMI (weight in kg/height2). Correlation analysis will also be undertaken with other laboratory parameters.	January-June 2020
Secondary	Collecting Covid-19 screening results together with age, sex, ethnicity and BMI and other relevant laboratory results.	All Covid-19 screening results together with vitamin D (nmol/L), ethnicity, age (yrs), weight (m) and height to obtain BMI, length of stay in hospital including ICU in days (if applicable), type of illness, recovered or not (y or no), associated health conditions, CRP, Ferritin, Haematinics, vitamin A and E, procalcitonin, LDH, INR, fibrinogen, FBC, D-dimers, CK, Troponin-T, cytokines, renal function and electrolytes will be collected from patients tested at GSTT NHS Trust.; We expect that only a small number of patients who had Covid-19 screening performed would have had vitamin D, cytokines and other markers measured. However, we estimate that we will be able to identify a sufficient number of Covid-19 patients for regression and correlation analysis from this data.	March-June 2020

External Links

•   Abstract presented at XII Immunonutrition Conference in
•   Abstract presented at XII Immunonutrition Conference in Barcelona